By James Foran, MD
2008-12-08
In a coup for platelets everywhere (or more accurately, for a lack of platelets), Dr. Francesco Zaja, from the University of Udine in Italy, presented abstract #1 at yesterday’s Plenary Session with his study of rituximab in idiopathic thrombocytopenic purpura (ITP). This marks the second year in a row that a randomized study on ITP has been presented at the Plenary Session of ASH. In this prospective randomized study, he found that the addition of rituximab to a therapeutic pulse of dexamethasone significantly improved the long-term rate of sustained response for ITP (platelets >50 x 109/L at 6 months) at 85 percent, more than double the rate of dexamethasone alone (39%). Importantly, even after failure of dexamethasone alone in 27 patients (defined as platelets <20 x 109/L within 6 months), salvage therapy with rituximab and dexamethasone was effective with a sustained response in more than half of the latter group.
Dr. Zaja and his colleagues stopped the trial, initiated in 2005, early after a planned interim analysis in n=101 randomized ITP patients, when a significant advantage in sustained responses was demonstrated in favor of the rituximab arm. He found that the treatment was well tolerated, and there was no substantial difference in safety profile between the two arms. Similar results were apparent when the results were analyzed on both the strict “per protocol” criteria, as well as on an “intention to treat” analysis.
Dr. Zaja found that the benefit with the addition of rituximab to dexamethasone for ITP therapy appears to be durable. In follow-up of sustained responders, at a median period of observation of 18 months (beyond the initial 6 months), loss of response occurred in only 11 percent of those who had received rituximab as either first-line or salvage therapy, compared to a 25 percent rate of loss of sustained response in the dexamethasone alone arm. Dr. Zaja noted that rituximab “… changes the natural history of ITP …,” and observed that unlike other new or available treatments for ITP, rituximab may indeed have a curative effect on the disease based on the durability of the responses. Based on these results, he advised that rituximab therapy should be considered before splenectomy, particularly in patients with higher surgical risk.
Asked about his plans for further studies of rituximab in ITP, Dr. Zaja stated that he and his colleagues are now exploring lower doses of rituximab. Interestingly, Dr. Zaja reported that “… the serum concentration of rituximab did not correlate with the rate of response,” and their preliminary studies suggest that lower rituximab doses are also active in ITP. In addition, Dr. Zaja noted that correlative studies that they performed demonstrated a return-to-normal of the T-cell subsets after rituximab therapy, suggesting a role for both B cells and T cells and an interaction between them in ITP.
In introducing abstract #1, Dr. James George, of the University of Oklahoma (themselves ranked #2!), noted that the goal in ITP is attaining a “safe durable platelet count with minimal or no side effects.” The report of sustained responses with first-line rituximab is great news for ITP patients. In particular, the prospect of durable remissions that may obviate the need for splenectomy is likely to change the early management of this disease. Updates on other thrombopoietic agents which show benefit in chronic ITP include eltrombopag (abstracts #400 & 401) and romiplostim (abstract #402), which will be presented later this morning in the ITP oral sessions (Moscone West, Room 3007).
Dr. Foran indicated no relevant conflicts of interest.
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